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Inhibition of14C-Aminopyrine accumulation in isolated rabbit gastric glands by the H2-receptor antagonist HOE 760 (TZU-0460)

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Abstract

Acid secretion in isolated rabbit gastric glands was measured by means of the14C-aminopyrine accumulation technique. Hoe 760 (TZU-0460) and Hoe 062, the desacetylated compound of Hoe 760, caused a concentration-dependent reduction of histamine (100 μM) induced aminopyrine-accumulation. The IC50-values were 3.16±0.84 μM (n=5) and 1.58±0.6 μM (n=6) for Hoe 760 and Hoe 062, respectively. In comparison an IC50 of 9.0±0.72 μM (n=6) was obtained for cimetidine and 3.3±1.4 μM (n=5) for ranitidine. The IC50-values of ranitidine, Hoe 760 and Hoe 062 were significantly different (p<0.05) from cimetidine. The addition of increasing concentrations of Hoe 760 to the histamine concentration-response curve caused a parallel rightward shift. The transformation of these concentration-response curves according to Arunlakshana and Schild indicated that this inhibition was caused by a competitive antagonism of the histamine receptor on the parietal cell. In agreement with these findings the dbc-AMP stimulated aminopyrine accumulation remained unaffected by the H2-receptor antagonists.

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Authors and Affiliations

  1. Department of Pharmacology, Hoechst AG, P.O. Box 80 03 20, D-6230, Frankfurt/Main, Germany FR

    A. W. Herling, M. Becht, M. Becht, M. Ljungström & M. Bickel

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  1. A. W. Herling
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  2. M. Becht
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  3. M. Becht
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  4. M. Ljungström
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  5. M. Bickel
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Herling, A.W., Becht, M., Becht, M. et al. Inhibition of14C-Aminopyrine accumulation in isolated rabbit gastric glands by the H2-receptor antagonist HOE 760 (TZU-0460). Agents and Actions 20, 35–39 (1987). https://doi.org/10.1007/BF01965623

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  • DOI: https://doi.org/10.1007/BF01965623

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